1. Field of the Invention
The invention relates to artificial neural networks, and apparatus, articles and methods involving artificial neural networks.
2. Related Art
The dentate gyrus (DG) is one of two brain regions with substantial neurogenesis throughout the lifetime of mammals (Altman and Das, 1965; Eriksson et al., 1998). In rats, thousands of new granule cells (GC) are born into the existing circuitry every day (Cameron and McKay, 2001), though only a fraction of these cells survive to become fully functional neurons (Kempermann et al., 2003). Each newborn neuron undergoes a maturation process lasting several months, developing electrical properties that are highly similar to developmentally born GC and forming synaptic contacts with the same afferent and efferent neurons (Esposito et al., 2005; van Praag et al., 2002; Zhao et al., 2006). While these adult-born neurons ultimately appear identical to those born in utero and post-natally, the maturation process progresses through states that make immature neurons distinct from mature GC. The integration of new neurons into the existing circuitry involves complex mechanisms for synaptogenesis (Toni et al., 2008; Toni et al., 2007) and is accompanied by distinct physiological properties, including lower threshold and higher amplitude long-term potentiation (LTP) (Ge et al., 2007; Schmidt-Hieber et al., 2004) and potentially greater excitability (Esposito et al., 2005). Furthermore, there is a pronounced relationship between behavior and neurogenesis. Physical activity, environmental enrichment, and learning increase proliferation and survival of new neurons (Gould et al., 1999; Kempermann et al., 1997; van Praag et al., 1999) whereas age and stress adversely affect the neurogenesis process (Gould et al., 1991; Kuhn et al., 1996). Anti-depressants have been shown to stimulate proliferation and require neurogenesis for their function (Sahay and Hen, 2007). The regulation of survival appears to be particularly dependent on activity, as new neurons pass through a critical period for survival that requires NMDA activation and that benefits strongly from environmental enrichment (Tashiro et al., 2007; Tashiro et al., 2006).
Despite this increasing understanding of how new neurons integrate into the functional DG network, it is still unclear what the function of this process is. Computational studies have demonstrated how neurogenesis may affect memory formation (Aimone and Wiskott, 2008; Becker, 2005; Chambers et al., 2004; Deisseroth et al., 2004; Wiskott et al., 2006). While the functional implementation of neurogenesis differs greatly between models, ultimately most of these computational results suggest that, without this addition of new neurons, new information might be encoded in a manner that disrupts previous memories. Conversely, numerous behavioral studies (using a range of knockdown techniques) investigating the role of new neurons on several different hippocampal memory tasks have reported mixed results (Leuner et al., 2006). For example, at least three separate studies have demonstrated that rodents with reduced neurogenesis showed impaired performance on the Morris water maze (Dupret et al., 2008; Snyder et al., 2005; Zhang et al., 2008), but no differences in water maze performance were seen in several other studies using different (and in one case the same) knockdown techniques (Saxe et al., 2006; Shors et al., 2002).
The difficulty in observing a strong knockdown phenotype on classic hippocampal memory tasks, combined with the observation that the DG may only be required for certain hippocampus-dependent behaviors (McHugh et al., 2007; Nakashiba et al., 2008), suggests that neurogenesis may not be critical to many of the functions that the hippocampus has classically been assigned. Rather than suggesting that neurogenesis has no cognitive relevance, it is important to consider an alternative: that new neurons provide functions that have not previously been described for the hippocampus. For example, in a recent communication, the inventors described a hypothesis for how immature neurons may alter the DG's function of reducing similarity between information sent to the hippocampus (i.e., pattern separation) by being more active than fully mature GC. Such increased participation over transient periods could be the source of the temporal associations seen in long-term memory (Aimone et al., 2006).